Drug & supplement interaction

Nattokinase + Pentoxifylline

Pentoxifylline brand name: Trental.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Nattokinase has a moderate interaction with Pentoxifylline. Nattokinase might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Nattokinase and Pentoxifylline

Here is the interaction we found between these two, with the evidence behind it.

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

Why this applies to Pentoxifylline

Pentoxifylline falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Nattokinase interacts with.

Nattokinase might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
Nattokinase has thrombolytic and anticoagulant effects. There is a case report of intracranial hemorrhage in a patient who added nattokinase to aspirin therapy.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing about pairing these two: pentoxifylline (Trental) already works by thinning your blood a bit so it flows more easily through small vessels. Nattokinase also nudges things in that same direction by helping break down clots. So when you combine them, you're stacking two blood-thinning effects on top of each other, which could raise your bleeding risk. That might show up as easy bruising, nosebleeds, bleeding gums, or bleeding that takes longer to stop.

I'll be honest with you about the evidence here: it's on the weaker side, mostly lab and animal data plus one case report involving aspirin, not pentoxifylline directly. So this isn't a guaranteed problem. Still, since both lean the same way, please check with your pharmacist or doctor before adding nattokinase rather than starting it on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Suzuki Y, Kondo K, Matsumoto Y, et al. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci 2003;73:1289-98.. PubMed
  2. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enchancement of fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84:139-43.
  3. Chang, Y. Y., Liu, J. S., Lai, S. L., Wu, H. S., and Lan, M. Y. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med 2008;47(5):467-469. PubMed
  4. Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep 2015;5:11601. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Nattokinase Also Interacts With Other Medications

Nattokinase has 288 moderate known drug interactions in our database — the Pentoxifylline one above is one of them. If you take anything else, check it against the full list below.

Moderate 288 No known interaction 2,542 (incl. Pentoxifylline)
Taking anything else?

Check Another of Your Medications Against Nattokinase

Covers the 2,830 medications we’ve checked against Nattokinase. Pick one to open its full report.

From our Q&A

Questions About Nattokinase or Pentoxifylline

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Nattokinase or Pentoxifylline, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Pentoxifylline

This page covers Nattokinase only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Pentoxifylline page lists 218 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Danshen (major), Piracetam (major), Aconite (moderate) and Allspice (moderate).

By severity: 3 major · 190 moderate · 25 minor.

From our pharmacist’s overview on the Pentoxifylline page

“Pentoxifylline (Trental) improves blood flow in people with poor leg circulation partly by making platelets less sticky, so treat this list as one to read carefully rather than skim. Of the 218 supplements on file, 202 can also slow clotting, which means adding them stacks bleeding risk on bleeding risk.”

Reviewed by 2 · Jul 18, 2026

Open the Pentoxifylline interaction page

One more smart check

Taking Nattokinase as Part of a Dietary Supplement Product? Check It for Interactions

We hold 509 real supplement products containing Nattokinase, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Nattokinase. Your product may carry other ingredients that interact with Pentoxifylline too, on top of Nattokinase — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Nattokinase and Pentoxifylline Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Nattokinase
Top 25%

#245 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Pentoxifylline
Top half

#886 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Nattokinase

What is Nattokinase?

Nattokinase
  • Heart and circulatory health
  • Blood clot prevention
  • High blood pressure
  • Improving blood flow
  • Cholesterol support

Nattokinase is an enzyme from the fermented soybean food natto that may have mild blood-thinning and blood-flow effects. Some small studies hint at benefits for blood pressure and circulation, but the evidence is limited and more research is needed. Because it can affect clotting, talk to your pharmacist or doctor before trying it, especially if you take medicines or have a bleeding risk.

Read the full Nattokinase monograph & all interactions
Medication

About Pentoxifylline

What Is Pentoxifylline Used For?

Brand name: Trental

Pentoxifylline Extended-Release Tablets are used to treat intermittent claudication — leg pain, cramping, or fatigue that happens during walking because narrowed arteries aren't delivering enough blood to the muscles. The underlying cause is chronic occlusive arterial disease, a condition where the arteries in the limbs become blocked or narrowed over time.

Pentoxifylline can help improve walking distance and reduce symptoms, but it is not a substitute for procedures that physically open or bypass blocked arteries when those treatments are needed.

See full Pentoxifylline drug information
Keep checking

Other Drugs & Nattokinase

Browse every other medication we’ve checked against Nattokinase — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
288Moderate
0Minor
2,541No known interaction
288 Moderate 2,541 No interaction
Moderate

288 interactions

Showing 60 of 288 moderate interactions — see all 288 on the Nattokinase page.

No interaction 2,541 drugs checked — show the list

We also checked Nattokinase against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,541 medications checked with no known interaction — see the full Nattokinase list.

See the full Nattokinase interactions page
See every supplement checked against Pentoxifylline, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Nattokinase monograph › Uses, safety, and every drug interaction in one place Pentoxifylline supplement interactions › Every supplement checked against Pentoxifylline, ranked by severity Pentoxifylline drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Nattokinase and Pentoxifylline Together: Common Questions

Can you take Nattokinase with Pentoxifylline?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Nattokinase and Pentoxifylline interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Pentoxifylline and Nattokinase?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.